清肝化痰活血方对大鼠非酒精性脂肪性肝炎的防治作用
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摘要
目的:探讨清肝化痰活血方对LXRa/FAS信号通路介导的非酒精性脂肪性肝炎(NASH)大鼠肝细胞脂肪沉积的影响。方法:选用SPF级雄性SD大鼠70只,分4组,正常组、模型组、治疗组及预防组;除正常组外其余3组大鼠采用高脂饮食复制NASH模型;造模8周结束。预防组大鼠从造模开始给予清肝化痰活血方灌胃,1次/d,共12周;治疗组大鼠从造模结束后,开始灌胃清肝化痰活血方,而模型组、正常组大鼠灌胃等量生理盐水,均1次/d,共4周。观察各组大鼠肝脏脂肪变性程度、血清ALT、AST、TC、TG水平。采用实时定量PCR法检测肝细胞LXRamRNA、FAS mRNA的表达。结果:造模8周时,正常组大鼠肝组织正常,其余3组大鼠肝脏均发生不同程度脂肪变性;模型组大鼠血清ALT、AST水平升高,与正常组比较,差异有显著性意义(P<0.05),与模型组比较,预防组大鼠血清ALT、AST、TC、TG水平显著下降(P<0.05);治疗组大鼠的肝脏脂肪变性程度均明显轻于模型组大鼠,其ALT、AST、TC、TG水平明显低于模型组(P<0.05);与正常组比较,其余3组大鼠肝细胞LXRa、FAS基因表达水平均明显升高(P<0.01),与模型组比较,预防组和治疗组大鼠的上述基因表达水平下调明显(P<0.01)。结论:LXRa/FAS通路是介导NAFLD脂质平衡代谢紊乱重要的信号通路,清肝化痰活血方能够调控肝细胞LXRa/FAS通路,使NASH大鼠肝细胞脂肪沉积趋于减轻,这可能是该方抗实验性大鼠脂肪性肝炎的作用机制之一。
Objective:To investigate the effects of Qinggan huatan huoxue Recipe on Nonalcoholic fatty liver disease in rats(NAFLD).Methods:Seventy SPF-class male SD rats were selected and divided into 4 groups:normal group,model group,treatment group and prevention group; In addition to the normal group,NAFLD rat models were replicated with high fat diet in all groups.Eight weeks of makeover.The rats in the prevention group were given the Qinggan huatan huoxue recipe method to fill their stomachs from the start of moulding.The rats in the treatment group began to pour stomach to Qinggan huatan huoxue recipe after moulding.In the model group and normal group,the same amount of saline was injected into the stomach.All once a day for 12 weeks.To observe the levels of serum ALT,AST,TC and TG were observed.The expression of LXRamRNA and FAS mRNA in hepatocytes were detected by real time quantitative PCR method.Results:The normal liver tissue of rats was normal at 8 weeks.The rats in the model group had different degrees of fat degeneration.Compared with normal rats,the serum ALT and AST levels in the model group had an upward trend.After comparison,they had significant significance(P<0.05); Compared with the model group,serum ALT,AST,TC and TG levels decreased significantly in the prevention group(P<0.05); The degree of liver fatty degeneration in the treatment group was significantly lower than that in the model group.The levels of ALT,AST,TC,and TG in the treatment group were significantly lower than those in the model group(P<0.05); Compared with the normal group,the expression of LXRa and FAS genes in the model group increased significantly(P<0.01); Compared with the model group,the expression of the above gene were significantly reduced in the prevention group and the treatment group(P<0.01).Conclusion:The LXRa-FAS pathway is an important signal pathway to mediate the metabolic disorder of NAFLD lipid balance,and the LXRa-FAS pathway of liver cells can be regulated by Qinggan huatan huoxue recipe.This may be one of the mechanisms of action of this party against experimental rat fatty liver.
Objective:To investigate the effects of Qinggan huatan huoxue Recipe on Nonalcoholic fatty liver disease in rats(NAFLD).Methods:Seventy SPF-class male SD rats were selected and divided into 4 groups:normal group,model group,treatment group and prevention group; In addition to the normal group,NAFLD rat models were replicated with high fat diet in all groups.Eight weeks of makeover.The rats in the prevention group were given the Qinggan huatan huoxue recipe method to fill their stomachs from the start of moulding.The rats in the treatment group began to pour stomach to Qinggan huatan huoxue recipe after moulding.In the model group and normal group,the same amount of saline was injected into the stomach.All once a day for 12 weeks.To observe the levels of serum ALT,AST,TC and TG were observed.The expression of LXRamRNA and FAS mRNA in hepatocytes were detected by real time quantitative PCR method.Results:The normal liver tissue of rats was normal at 8 weeks.The rats in the model group had different degrees of fat degeneration.Compared with normal rats,the serum ALT and AST levels in the model group had an upward trend.After comparison,they had significant significance(P<0.05); Compared with the model group,serum ALT,AST,TC and TG levels decreased significantly in the prevention group(P<0.05); The degree of liver fatty degeneration in the treatment group was significantly lower than that in the model group.The levels of ALT,AST,TC,and TG in the treatment group were significantly lower than those in the model group(P<0.05); Compared with the normal group,the expression of LXRa and FAS genes in the model group increased significantly(P<0.01); Compared with the model group,the expression of the above gene were significantly reduced in the prevention group and the treatment group(P<0.01).Conclusion:The LXRa-FAS pathway is an important signal pathway to mediate the metabolic disorder of NAFLD lipid balance,and the LXRa-FAS pathway of liver cells can be regulated by Qinggan huatan huoxue recipe.This may be one of the mechanisms of action of this party against experimental rat fatty liver.
引文
[1] Latea L,Negrea S,Bolboaca S. Primary non-alcoholic fatty liver disease in hypertensive patients[J].Austr MedJ,2013,6( 6) :325-330.
[2] Tan TC,Crawford DH,Jaskowski LA,et al. Altered lipid metabolism in Hfe-knockout mice promotes severe NAFLD and early fibrosis[J].Am J Physiol Gastrointest LiverPhysiol,2011,301(5) :865-876.
[3] Musso G,Gambino R,Cassader M.Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease( NAFLD) [J]. Prog Lipid Res,2009,48(1) :1-26.
[4] Yap F,Craddock L,Yang J. Mechanism of AMPK suppression of LXR dependent Srebp-1 transcription[J].IntJ Biol Sci,2011,7( 5) :645 -650.
[5] 高鑫.肝脏脂肪沉积是代谢紊乱的启动因素[J].中华医学杂志,2011,91(26):1803-1804.
[6] 杜娆,谢梅林.肝细胞内脂质平衡机制及其调节药物的研究进展[J].中国药理学与毒理学杂志,2013,27( 4) :755-759.
[7] 王冰,程丽静,高政南,等.肝X 受体的激活对小鼠糖尿病肝脏脂肪酸合成酶表达的调节[J].中华医学杂志,2008,88( 12) :848-852.
[8] 毛奇琦,孙旭.核受体在胆汁酸和胆固醇代谢中的作用[J].国际消化病杂志,2008,28( 3) :243-245.
[9] 叶放,赵文霞.中医对非酒精性脂肪肝的认识现状[J].中国中西医结合消化杂志,2003,11(1):60.
[10] 范建高,曾民德.脂肪性肝病[ M] .北京:人民卫生出版社,2005:336.
[2] Tan TC,Crawford DH,Jaskowski LA,et al. Altered lipid metabolism in Hfe-knockout mice promotes severe NAFLD and early fibrosis[J].Am J Physiol Gastrointest LiverPhysiol,2011,301(5) :865-876.
[3] Musso G,Gambino R,Cassader M.Recent insights into hepatic lipid metabolism in non-alcoholic fatty liver disease( NAFLD) [J]. Prog Lipid Res,2009,48(1) :1-26.
[4] Yap F,Craddock L,Yang J. Mechanism of AMPK suppression of LXR dependent Srebp-1 transcription[J].IntJ Biol Sci,2011,7( 5) :645 -650.
[5] 高鑫.肝脏脂肪沉积是代谢紊乱的启动因素[J].中华医学杂志,2011,91(26):1803-1804.
[6] 杜娆,谢梅林.肝细胞内脂质平衡机制及其调节药物的研究进展[J].中国药理学与毒理学杂志,2013,27( 4) :755-759.
[7] 王冰,程丽静,高政南,等.肝X 受体的激活对小鼠糖尿病肝脏脂肪酸合成酶表达的调节[J].中华医学杂志,2008,88( 12) :848-852.
[8] 毛奇琦,孙旭.核受体在胆汁酸和胆固醇代谢中的作用[J].国际消化病杂志,2008,28( 3) :243-245.
[9] 叶放,赵文霞.中医对非酒精性脂肪肝的认识现状[J].中国中西医结合消化杂志,2003,11(1):60.
[10] 范建高,曾民德.脂肪性肝病[ M] .北京:人民卫生出版社,2005:336.